文章摘要

微卫星不稳定和RAS基因突变与III~IV期大肠癌预后的相关性

作者: 1孙屏, 1郭兴美, 1吕慧, 1徐蓉蓉
1 南京医科大学附属无锡第二医院病理科,江苏 无锡 214002
通讯: 吕慧 Email: sspingsun053169@163.com
DOI: 10.3978/j.issn.2095-6959.2020.10.012
基金: 无锡市卫健委科研项目(MS201930)。

摘要

目的:探讨III~IV期大肠癌患者微卫星不稳定性(microsatellite instability,MSI)状态和RAS基因突变与临床病理特征及预后的关系。方法:检测202例III~IV期大肠癌组织中KRAS,NRAS和BRAF基因突变情况以及MSI状态,分析不同临床病理参数组别的基因突变情况与预后的关系。结果:202例III~IV期结直肠癌(colorectal cancer,CRC)中KRAS基因突变,BRAF突变和高度微卫星不稳定性(microsatellite instability-high,MSI-H)肿瘤主要发生在右半结肠,伴有黏液腺癌的肿瘤中,而p53突变更多发生在直肠,不伴有黏液腺癌的肿瘤中。单因素分析显示III期CRC中,RAS突变型与野生型相比,无进展生存时间(progression-free survival time,PFS)显著缩短(HR:1.804,95%CI:1.159~2.808;P=0.009),在III期CRC中,双野生型组(KRAS,NRAS,BRAF3个基因中有1个突变的)与3个基因均是野生型的比较,PFS显著缩短(HR:1.962,95%CI:1.254~3.071;P=0.003)。同样,在多因素分析时,III期CRC中RAS和BRAF均为野生型的患者,PFS与带有任一突变型的相比显著延长(HR:1.962,95%CI:1.253~3.071;P=0.003)。而单因素、多因素分析,均未发现RAS突变、BRAF突变各亚组间总生存时间(overall survival time,OS)有统计学差异。结论:RAS,BRAF突变以及MSI状态对III~IV期大肠癌预后有一定的预测作用,有待于大样本以及精细分组后的验证。
关键词: 大肠癌;III~IV期;MSI;RAS基因;预后

Relationship between microsatellite instability, RAS gene mutation and prognosis of stage III–IV colorectal cancer

Authors: 1SUN Ping, 1GUO Xingmei, 1LÜ Hui, 1XU Rongrong
1 Department of Pathology, The Second Affiliated People’s Hospital of Wuxi, Nanjing Medical University, Wuxi Jiangsu 214002, China

CorrespondingAuthor: LÜ Hui Email: sspingsun053169@163.com

Foundation: This work was supported by Wuxi Health Commission Scientific Research Project, China (MS201930).

Abstract

Objective: To investigate the relationship between RAS gene mutation, microsatellite instability (MSI) status and clinicopathological features and prognosis in patients with colorectal cancer. Methods: KRAS, NRAS and BRAF gene mutations and MSI status were examined in 202 patients with colorectal cancer. Statistical methods were used to analyze the relationship between gene mutations with clinicopathological features and prognosis in different groups, such as age, sex, tumor size, degree of differentiation, and so on. Results: KRAS gene mutation, BRAF gene mutation and microsatellite instability-high (MSI-H) tumor mainly occurred in the right colon with mucinous adenocarcinoma, while p53 mutation occurred more frequently in rectal tumors without mucinous adenocarcinoma. Univariate analysis showed that the progression-free survival time (PFS) of the RAS mutant in stage III CRC was significantly shorter than that of the wild type (HR: 1.804, 95%CI: 1.159 to 2.808; P=0.009). In the stage III CRC, the PFS of the double wild type group (one of the three genes KRAS, NRAS, BRAF) was significantly shorter than that of all three wild types (HR: 1.962, 95%CI: 1.254 to 3.071; P=0.003). Similarly, in multivariate analysis, both RAS and BRAF in stage III CRC were wild type, PFS was significantly longer than that in patients with any mutant type (HR: 1.962, 95%CI: 1.253 to 3.071; P=0.003). However, univariate and multivariate analysis showed that there was no significant difference in overall survival (OS) time among RAS mutation and BRAF mutation subgroups. Conclusion: RAS, BRAF mutation and MSI status can predict the prognosis of stage III and IV colorectal cancer, which need to be verified by large sample size and fine grouping.
Keywords: colorectal cancer; stage III to IV; MSI; RAS gene; prognosis